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Advanced cholangiocarcinoma continues to harbor a difficult prognosis and therapeutic options have been limited. During the course of a clinical trial of whole genomic sequencing seeking druggable targets, we examined six patients with advanced cholangiocarcinoma. Integrated genome-wide and whole transcriptome sequence analyses were performed on tumors from six patients with advanced, sporadic intrahepatic cholangiocarcinoma (SIC) to identify potential therapeutically actionable events. Among the somatic events captured in our analysis, we uncovered two novel therapeutically relevant genomic contexts that when acted upon, resulted in preliminary evidence of anti-tumor activity. Genome-wide structural analysis of sequence data revealed recurrent translocation events involving the FGFR2 locus in three of six assessed patients. These observations and supporting evidence triggered the use of FGFR inhibitors in these patients. In one example, preliminary anti-tumor activity of pazopanib (in vitro FGFR2 IC50≈350 nM) was noted in a patient with an FGFR2-TACC3 fusion. After progression on pazopanib, the same patient also had stable disease on ponatinib, a pan-FGFR inhibitor (in vitro, FGFR2 IC50≈8 nM). In an independent non-FGFR2 translocation patient, exome and transcriptome analysis revealed an allele specific somatic nonsense mutation (E384X) in ERRFI1, a direct negative regulator of EGFR activation. Rapid and robust disease regression was noted in this ERRFI1 inactivated tumor when treated with erlotinib, an EGFR kinase inhibitor. FGFR2 fusions and ERRFI mutations may represent novel targets in sporadic intrahepatic cholangiocarcinoma and trials should be characterized in larger cohorts of patients with these aberrations.

To assess the role of stimulus speed and order on the predatory behaviors of the praying mantis Sphodromantis lineola (Burr.), tethered adult females were presented with various flat black stimuli (lures) by means of a variable speed mechanical arm. Lure speed had a dramatic effect on mantis behavior: mantises emitted significantly more strikes to a 6 x 6 mm square and to 'worm' lures (i.e. length > width = 6 mm) moving at 34.3 cm/sec than they did to 'antiworm' lures (i.e. width > length = 6 mm), or to slower moving lures. These effects were consistent over lure directions (0-75 degrees relative to the mantis' long axis), and background patterns. On the other hand, mantises emitted significantly more approaching behavior to lures moving at 12 cm/sec than to lures moving at 36 cm/sec. This suggests that S. lineola extract distance information from retinal image velocity, as do other insects. Stimulus order also effected mantis predatory behavior: for instance, mantises were more likely to track a lure without striking at it on the first trial than on subsequent trials. However, after the first trial, they were also more likely to freeze (become immobile) when a lure was presented. Mantises were also less likely to strike at a preferred lure if it was preceded by one or two non-preferred lures. In a final experiment, intact, freely moving mantises were placed in an arena, presented with adult crickets, and video taped. The behaviors of the freely moving mantises were congruent with those of the tethered mantises in the previous experiments. This series of experiments demonstrates that the information processing capabilities of S. lineola are more complex than generally depicted, however, they can be explained by assuming a neural organization similar to that of other insects such as flies (Diptera) and dragonflies (Odonata).

The 25 years of rising cesarean delivery rates in the United States may have finally run their course. In 1989 the rate of 23.8 cesareans per 100 deliveries was not significantly different from 24.7 in 1988, 24.4 in 1987, or 24.1 in 1986. The 1989 primary rate of 17.1 first cesareans per 100 women with no previous cesarean was also not significantly different from 17.5 for 1988, or 17.4 for 1987 and 1986. The percentage of vaginal births after cesarean section per 100 deliveries showed a remarkable rise between 1988 and 1989--from 12.6 percent in 1988 to 18.5 percent in 1989. Data are from the National Hospital Discharge Survey conducted by the National Center for Health Statistics, Centers for Disease Control.

The 1988 National Maternal and Infant Health Survey was conducted by the National Center for Health Statistics to study factors related to poor pregnancy outcome, such as adequacy of prenatal care; inadequate and excessive weight gain during pregnancy; maternal smoking, drinking, and drug use; and pregnancy and delivery complications. The survey is a nationally representative sample of 11,000 women who had live births, 4000 who had late fetal deaths, and 6000 who had infant deaths in 1988. Mothers were mailed questionnaires based on information from certificates of live birth, reports of fetal death, and certificates of infant death. Information supplied by the mother, prenatal care providers, and hospitals of delivery was linked with the vital records to expand knowledge of maternal and infant health in the United States. Data collection from the Longitudinal Followup of mothers in the survey began in January 1991. It provides information on health and development of low- and very low-birthweight babies, child care and safety, maternal health, maternal depression, and plans for adoption and foster care. Both surveys will provide useful data for clinicians in maternal and child health.

Many women use commercially available home pregnancy tests to determine their pregnancy status before seeking professional health care. Despite the increasing popularity of these products, no national estimates have been reported to date on their frequency of use. We analyzed available data from the 1988 National Maternal and Infant Health Survey to determine the frequency of use of home pregnancy tests during recent pregnancies of women of varying sociodemographic backgrounds. Approximately 33 percent (N = 4700) of the women surveyed used such a device. Use was most frequent among women who were white, married, over age 39 years, highly educated, or had a high family income. We conclude that home pregnancy testing appears to be a frequent procedure, especially among women of high socioeconomic background.

Obstetrical technologies such as electronic fetal monitoring (EFM) and selected diagnostic imaging procedures can be integral components of perinatal care. The Center for Devices and Radiological Health, a unit within the Food and Drug Administration, collaborated with the National Center for Health Statistics in the design and conduct of a National Maternal and Infant Health Survey to collect information from prenatal care providers, hospitals, and mothers on the use of EFM, diagnostic ultrasound, and x-ray examinations during pregnancy, labor, and delivery. A pretest, conducted some months before the survey began, showed that 78.8% of the pregnancies surveyed received a diagnostic ultrasound examination during pregnancy. Approximately 58.3% of the ultrasound-exposed mothers had two or more such examinations. Approximately 10.1% of the ultrasound examinations were performed in the first trimester of pregnancy, 57.0% in the second trimester, and 32.9% in the third trimester. The most common indication for an ultrasound examination was to establish dates or gestational age. Approximately 15.3% of the pregnancies surveyed received an x-ray examination. Approximately 74.6% of the pregnancies were monitored with EFM during labor. External EFM was used alone during 54.9% of the labors and along with internal EFM during 19.7% of the labors. The implications of these pretest findings are discussed, along with a review of the medical literature on the safety and effectiveness of these medical device technologies.

Medical devices and diagnostic imaging procedures such as ultrasound, X-rays, and electronic fetal monitoring devices are used in the medical care of many pregnant women today. The responsibility for the safety and effectiveness of these diagnostic technologies is shared by a number of Public Health Service agencies, one of which is the Center for Devices and Radiological Health (CDRH), a unit within the Food and Drug Administration. The CDRH collaborated with the National Center for Health Statistics (NCHS) in conducting a study of recent trends in the uses of diagnostic ultrasound, medical X-rays, and electronic fetal monitoring devices in the medical care of pregnant women. This study used data from the 1980 National Natality and Fetal Mortality Surveys and the 1987 pretest to the National Maternal and Infant Health Survey. Hospitals and prenatal care providers of the pregnant women contributed information regarding the use of these medical devices. Between 1980 and 1987, ultrasound use more than doubled, increasing from 33.5 percent of pregnancies in 1980 to 78.8 percent in 1987 (P less than 0.001). More ultrasound examinations were performed earlier in gestation in 1987 than in 1980, with 10.1 percent being performed during the first trimester in 1987, compared with 6.9 percent in 1980 (P less than 0.001). Use of external electronic fetal monitoring devices during delivery also increased significantly between 1980 and 1987, from 33.5 percent to 74.6 percent (P less than 0.001). Use of medical X-rays among women with live births remained relatively unchanged, 15.0 percent in 1980 and 15.3 percent in 1987 (P = .282). The implications of these trends are discussed.

National Hospital Discharge Survey data, collected by the National Center for Health Statistics, were used to examine complications associated with cesarean and noncesarean deliveries in the years 1970 and 1978. Cesarean deliveries comprised 5.5 percent of all deliveries in 1970 and 15.2 percent in 1978. Two-thirds (68.4 percent) of the 1970 and 82.1 percent of the 1978 cesarean deliveries involved specified complications compared with only 14.6 percent of the 1970 vaginal deliveries and 17.8 percent of the 1978 vaginal deliveries. More than one-fourth of the 1970 and 1978 cesarean deliveries, but less than 1 percent of the vaginal deliveries, were preceded by a cesarean section delivery. From 1970 to 1978, there was both a rise in breech presentations and a shift toward surgical management of them. Also, cesarean deliveries were associated with placenta previa, fetopelvic disproportion, prolonged labor, and premature rupture of membranes. Several competing explanations have been offered for the rise in complication rates and in cesarean delivery rates.

Our study of cesarean rates in 19 industrialized countries of Europe, North America, and the Pacific revealed sharp differences in rates, ranging from a low of 5 (Czechoslovakia) to a high of 18 (United States) per 100 hospital deliveries in 1981. Differences in cesarean rates according to maternal age, parity, and complications of pregnancy and childbirth reflected national differences in obstetrical practice. For example, the percentage of mothers who had a vaginal birth after a previous cesarean section was only 5 in the United States as compared with 43 in Norway, where the cesarean rate was half that in the United States. Despite the wide range of cesarean rates, almost all the countries studied have had consistent increases over the past decade, and the annual rate of increase for all countries appears to be converging. The steady pace of increase in developed countries, combined with comparable or even higher rates of cesarean delivery now being reported in less developed countries, underscores the need for the medical community to consider the appropriateness of this continued rise in the number of cesarean deliveries.

Seven Public Health Service agencies collaborated with the National Center for Health Statistics in designing, funding, and analyzing the 1980 National Natality Survey (NNS) and 1980 National Fetal Mortality Survey (NFMS). The 1980 NNS-NFMS were nationally representative surveys based on samples of 9,941 live birth vital records and 6,386 fetal death vital records, which were weighted up to reflect U.S. estimates of 3,612,258 live births and 19,202 fetal deaths at 28 weeks' gestation or more. Four types of potential respondents who were associated with the sampled deliveries (married mothers, hospitals, attendants at delivery, and other medical providers of radiation procedures) were mailed eight-page questionnaires. The aim of the questionnaires was to expand our knowledge of the relationships of social, demographic, maternal health, infant health, and radiation characteristics to live births and late fetal deaths. The methods used in the NNS-NFMS are described in detail since seven other articles and the editorial in this issue are based on these surveys. The availability of other NNS-NFMS data is also discussed.

Data from the 1980 National Natality Survey (NNS) and the 1980 National Fetal Mortality Survey (NFMS) are used to describe the drinking and smoking behavior of married mothers before and during pregnancy according to maternal race and Hispanic origin, age, and education. Typically, smokers were white mothers under 25 years of age with a high school education or less, and drinkers were white mothers 25 years of age and older with more than a high school education. When pregnancy was confirmed, reductions in smoking and drinking occurred. However, mothers of stillborn infants were less likely to stop smoking than were the mothers of live-born infants. Although the prevalence of drinking was much higher than was the prevalence of smoking among the mothers included in these surveys, the reduction in drinking was much more pronounced than was the reduction in smoking. For nearly every sociodemographic subgroup, the prevalence of smoking was higher and the prevalence of drinking was lower among mothers of stillborn infants than among mothers of live-born infants. Some of these differences are due to the age-race-health status makeup of the two NNS-NFMS populations sampled, and carefully controlled multivariate analyses are required to specify the relationship of maternal smoking and drinking to birth outcome. This descriptive analysis is the first step in that process.

Today, low birth weight--weight less than 2,500 grams (5 pounds 8 ounces)--is recognized as the single most significant characteristic of the newborn associated with a greater risk of mortality and morbidity. This paper highlights maternal and infant health factors associated with low birth weight, using data from the 1972 and 1980 National Natality Surveys. Both surveys provide important information related to low birth weight that is not typically available from standard birth certificates and therefore not part of the usual natality vital statistics. In addition, induction of labor and cesarean section deliveries (first and repeat cesareans) were examined for 1980 to assess whether their use has exerted an influence on low birth weight.

In the 1980 National Natality and Fetal Mortality Surveys, information about fetal monitoring and type of delivery was obtained from hospitals for a sample of 9,941 live births and 6,386 fetal deaths of 28 weeks' gestation or more. Data in this analysis are weighted to provide national estimates of live births and late fetal deaths that occurred in U.S. hospitals during 1980. Electronic fetal monitoring (EFM) was used for 47.7 percent of live births; 27.2 percent were monitored by Doppler ultrasound only, 10.2 percent by scalp electrode only, 6.3 percent by Doppler ultrasound and scalp electrode only, and 4.0 percent by other methods and combinations. The distribution by type of EFM used was similar for the 42.7 percent of late fetal deaths (also called stillbirths) that were monitored. Variation in the use of EFM for live births and stillbirths is examined according to maternal age, parity, education, race, marital status, income, previous fetal loss, underlying medical conditions, complications of pregnancy, complications of labor, duration of labor, infant birth weight, and length of gestation. Among live births, 17.1 percent were delivered by cesarean section, as were 16.8 percent of stillbirths. The association between fetal monitoring and the primary cesarean section rate (the probability of cesarean section for women who had never had one) for all birth orders and for first births is examined according to characteristics of the mothers and the infants. Factors involved in the consistent association found between fetal monitoring and the primary cesarean section rate are discussed.

With National Hospital Discharge Survey data collected by the National Center for Health Statistics as a basis, rates of cesarean section deliveries were computed for the United States and its regions for 1970 through 1978. For each year and within each region, trends were examined according to variations in the mother's color, age, and marital status and in the hospital size (number of beds), the form of hospital ownership, and the length of the mother's hospital stay. Within each region and for each variable considered, cesarean section deliveries rose fairly uniformly. Nationally, C-sections comprised 5.5 percent of all deliveries in 1970, but rose steadily to comprise 15.2 percent of all deliveries in 1978. Overall, 1978 rates were highest in the Northeast, among whites, among women age 30 and over, among married women, in hospitals with 500 beds or more, and in proprietary hospitals. The mean length of the mother's hospital stay in 1978 was 6.7 days for cesarean section deliveries and 3.2 days for other deliveries, down from the mean hospital stay of 7.8 days for C-sections and 3.9 days for other deliveries observed in 1970.

The 1980 National Natality Survey (NNS) and 1980 National Fetal Mortality Survey (NFMS) provide a unique opportunity to examine variation in exposure to radiation during pregnancy for mothers of live-born and stillborn infants. Maternal race, age, education, and marital status in both surveys and low birth weight in the 1980 NNS are characteristics used to examine exposure rates for X-ray, ultrasound, nuclear medicine, shortwave, and microwave radiation examinations and treatments. About 15 percent of mothers of live infants and 23 percent of mothers who experienced stillbirths (fetal deaths of 28 weeks or more gestation) had a medical X-ray procedure during pregnancy. The 15 percent exposed in 1980 was a reduction from 22.5 percent of mothers exposed according to the results of the 1963 NNS; this reduction occurred in all race and age groups. About 34 percent of 1980 NNS mothers and 53 percent of 1980 NFMS mothers had ultrasound exposure during pregnancy. Radiation exposure rates were higher for 1980 NNS mothers who had low birth weight infants (under 2,500 g, or 5 lb, 8 oz) than for those who had normal weight infants.

The American Medical Record Association (AMRA) has worked closely with the National Center for Health Statistics (NCHS) in planning the 1988 National Maternal and Infant Health Survey (NMIHS). AMRA has endorsed the NMIHS and encourages the participation of hospital medical record departments.

Because of the multipurpose utility of followback surveys, six Public Health Service (PHS) agencies including the Bureau of Health Care and Delivery Assistance (BHCDA) financially assisted the National Center for Health Statistics (NCHS), which conducted the 1980 National Natality Survey (NNS) and 1980 National Fetal Mortality Survey (NFMS). These are called "followback" surveys because NCHS uses mail questionnaires and telephone to follow back informants (mothers, hospitals, and attendants at delivery) and medical sources of radiation named by informants, identified on Certificates of Live Birth and Reports of Fetal Death from all 52 state and independent registration areas of the United States. Ten basic data applications have emerged from the 1980 NNS/NFMS, and this paper addresses these 10 purposes simultaneously, in relation to NNS/NFMS uses in assessing obstetric technologies. The five obstetric technologies that are the focus of this paper are: cesarean delivery, electronic fetal monitoring, ultrasound, X-ray, and amniocentesis--and are often examined in relation to maternal complications and conditions. Data on these technologies are highlighted with reference to each of the following 10 data applications of followback surveys: produce national estimates of unique information; establish trends; facilitate analytic and epidemiologic research; use followback surveys as anchor data bases; undertake parallel studies; link followback surveys together to calculate new vital rates; conduct comparative studies vis-à-vis other data sets; assess volume of medical care; evaluate quality of information on vital records; and generate synthetic estimates and need assessments. Finally, this paper discusses NCHS plans to measure obstetric technologies in the 1988 National Maternal and Infant Health Survey, which will include natality, fetal mortality, and infant mortality components.